Sodium hydride → HCID 67499417, compound

HRID 1484750Notes

Reaction equation

HRID 1484750 reaction equation
[Cl:1][C:2]1[C:6]([NH:7][C:8](=[O:14])[CH:9]([CH3:13])[CH2:10][S:11][CH3:12])=[CH:5][N:4]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[N:3]=1.[H-].[Na+].Br[CH2:24][CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]>CN(C)C=O>[Si:27]([O:26][CH2:25][CH2:24][N:7]([C:6]1[C:2]([Cl:1])=[N:3][N:4]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[CH:5]=1)[C:8](=[O:14])[CH:9]([CH3:13])[CH2:10][S:11][CH3:12])([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 67500553HCID 67500553, compound

Product 1

HCID 67499417HCID 67499417, compoundYield 50.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamide (0.150 g, 0.483 mmol) in N,N-dimethylformamide (2.413 ml) was cooled to 0° C. Sodium hydride (0.039 g, 0.965 mmol, 60% dispersion) was added at and the reaction was stirred at 0° C. for 30 minutes. (2-Bromoethoxy)(tert-butyl)dimethylsilane (0.231 g, 0.965 mmol) was added, the ice bath was removed, and the reaction was stirred at room temperature for 2 hours. The reaction was heated at 65° C. for 1.5 hours and then cooled to room temperature. Brine was added and the mixture was extracted with dichloromethane. The combined organic phases were concentrated and chromatographed (0-100% ethyl acetate/hexanes) to give N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamide (0.120 g, 0.243 mmol, 50.4%) as an orange oil: IR (thin film) 1669 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.88 (d, J=2.5 Hz, 1H), 8.55 (dd, J=4.7, 1.4 Hz, 1H), 8.05 (s, 1H), 7.98 (ddd, J=8.3, 2.6, 1.4 Hz, 1H), 7.41 (ddd, J=8.4, 4.8, 0.5 Hz, 1H), 4.35-3.06 (m, 4H), 2.86-2.73 (m, 1H), 2.73-2.59 (m, 1H), 2.41 (dd, J=12.8, 5.7 Hz, 1H), 1.94 (s, 3H), 1.11 (d, J=6.7 Hz, 3H), 0.80 (s, 9H), 0.00 (s, 3H), −0.01 (s, 3H); ESIMS m/z 470 ([M+H]+).

Workup

  1. customthe ice bath was removed
  2. stirringthe reaction was stirred at room temperature for 2 hours
  3. temperatureThe reaction was heated at 65° C. for 1.5 hours
  4. temperaturecooled to room temperature
  5. additionBrine was added
  6. extractionthe mixture was extracted with dichloromethane
  7. concentrationThe combined organic phases were concentrated
  8. customchromatographed (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5ce100601da046b2b50d8072fe178b19
Source dataset
uspto-grants-2016_08
Patent number
US09422278B2

Reaction notes

Loading…